- Academic Publications
Distinguished Professor At Large
Nobel Laureate in Chemistry (2013)
Member of the USA National Academy of Sciences
Honorary Member of the Royal Society of Chemistry
PhD, MSc (The Weizmann Institute of Science)
BSc (Technion-Israel Institute of Technology)
Computer Simulation and Interpretation of the Properties of Large Molecules, with Special Emphasis on the Function of Biological Systems.
Prof. Warshel has authored over 390 peer-reviewed research articles, as well as a 1991 book entitled “Computer Modeling of Chemical Reactions in Enzymes and Solutions”. He also co-developed key computer programs for molecular simulations, which are now being widely used in different incarnations. Warshel and his coworkers have pioneered key approaches for simulating the functions of biological molecules, including introducing molecular dynamics in biology, developing the quantum mechanical/molecular-mechanical (QM/MM) approach, introducing simulations of enzymatic reactions, pioneering microscopic simulations of electron transfer and proton transfer processes in solutions and in proteins, pioneering microscopic modeling of electrostatic effects in macromolecules and introducing simulations of protein folding . He and his coworkers have elucidated recently the molecular origin of the vectorial action of molecular machines.
Prof. Warshel has been awarded the 2013 Nobel Prize in Chemistry; he is a Member of the USA National Academy of Sciences and an honorary member of the Royal Society of Chemistry. He also received numerous awards, including the Tolman Medal in 2003, the RSC 2012 Soft Matter and Biophysical Chemistry Award, and the 2014 Founders Award of the Biophysical Society.
1. S. Mukherjee, A. Warshel, Dissecting the role of the γ-subunit in the rotary-chemical coupling and torque generation of F1-ATPase. Proceedings of the National Academy of Sciences of the United States of America 112:2746-2751, 2015.
4. A. Warshel, Multiscale Modeling of Biological Functions: From Enzymes to Molecular Machines (Nobel Lecture). Angew. Chem. 53:10020-10031, 2014.
5. M.P. Frushicheva, M.J.L. Mills, P. Schopf, M.K. Singh, R.B. Prasad, A. Warshel, Computer Aided Enzyme Design and Catalytic Concepts. Curr. Opin. Chem. Biol. 21:56-62, 2014.
6. I. Kim, S. Chakrabarty, P. Brzezinski, A. Warshel, Modeling Gating Charge and Voltage Changes in Response to Charge Separation in Membrane Proteins. Proceedings of the National Academy of Sciences of the United States of America 111:11353-11358, 2014.
7. P. Schopf, A. Warshel, Validating Computer Simulations of Enantioselective Catalysis; Reproducing the Large Steric and Entropic Contributions in Candida Antarctica Lipase B. Proteins 82:1387-1399, 2014.
8. S. Vicatos, A. Rychkova, S. Mukherjee, A. Warshel, An Effective Coarse-Grained Model for Biological Simulations: Recent Refinements and Validations. Proteins 82:1168-1185, 2014.
9. S. Mukherjee, A. Warshel, Response to Vilfan: Constructing Structure-Based Free Energy Surfaces is the Key to Understand Myosin V Unidirectionality. Proceedings of the National Academy of Sciences of the United States of America 111:2077, 2014.
10. I. Kim, A. Warshel, Coarse-Grained Simulation of the Gating Current in the Voltage-Activation Kv1.2 Channel. Proceedings of the National Academy of Sciences of the United States of America 111:2128-2133, 2013.
- Academic Publications
PhD (University of Southern California)
Structure-dynamics- evolution relationship in proteins;Knotted proteins; Protein subcellular localization; Protein structure prediction; Disulfide proteins; Molecular simulation
Prof. Jenn-Kang Hwang got the Bachelor Degree at National Taiwan University, and Ph.D. at University of Southern California. Currently, he joind Chinese University of Hong Kang (ShenZhen) as a chair professor and executive vice president of Warshel Institute. In previously. he was the Director of the NCTU Center for Bioinformatic Research supported by MOE ATU Program 2nd phase. Additionally, he is one of the Editorial Board of Proteins: Structure, Function and Bioinformatics, and the International journal in Medical Engineering and Informatics since 2006, and served on the Editorial Board of Biochemical compounds, and the International journal of Medical Engineering and Informatics. Apart from his academic achievements, he also served as the president of Taiwan Society for Bioinformatics and Systems Biology, and the member of Biophysics Society.
Prof. Jenn-Kang Hwang is interested in the structure-dynamics- evolution relationship in proteins. Protein average thermal fluctuations are shown be derived directly from protein structures without assuming any mechanical models. A number of protein structural profiles such as residue packing, i.e. the weighted contact number (WCN), protein centroid distance, thermal fluctuation profile or smoothed solvent accessible surface profiles are similar to a smoothed version of sequence conservation profile in varying degrees. This is surprising, since the WCN profile is derived from a single protein structure, while the sequence conservation profile is derived from multiple sequence alignment of a group of homologous sequences. This suggests that a single protein structure contains evolutionary information that was previously derived only from multiple sequences. We are also interested in the following topics such as knotted proteins, protein subcellular localization, protein structure prediction, disulfide proteins, molecular simulation and any topics that are intellectually interesting.
1. Liu JW, Cheng CW, Lin YF, Chen SY, Hwang JK, SC Yen, Relationships between residue Voronoi volume and sequence conservation in proteins BBA – Proteins and Proteomics (2017) (accepted)
2. Liu JW, Lin JJ, Chen CW, Lin YF, Hwang JK, Huang TT, On the Relationship between Residue Structural Environment and Sequence Conservation in Proteins Proteins. 2017 Jun 9. doi: 10.1002/prot.25329
3. Liu KK, Qiu WR , Raj EN, Liu HF, Huang HS , Lin YW, Chang CJ, Chen TH, Chen C, Chang HC, Hwang JK, Chao JI Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway. Autophagy 2017 Jan 2;13(1):187-200. doi: 10.1080/15548627.2016.1254864
4. Chang CM, Huang YW, Lee CW, Huang TT, Shih CS, Hwang JK, Sequence Conservation, Radial Distance and Packing Density in Spherical Viral Capsids, PLoS one 2015 DOI: 10.1371/journal.pone.0132234.
5. Huang TT, Hwang JK, Chen CH, Chu CS, Lee Chi-Wen, Chen CC (PS)2: Protein Structure Prediction Server Version 3.0 Nucleic Acids Research 2015 43(W1):W338-42. doi: 10.1093/nar/gkv454.
6. Huang YW, Chang CM, Hwang JK The conservation profile of a protein bears the imprint of the molecule that is evolutionarily coupled to the protein Proteins 2015 83(8):1407-13. doi: 10.1002/prot.24809.
7. JJ Lin, ZL Lin, JK Hwang, TT Huang On the packing density of the unbound protein-protein interaction interface and its implications in dynamics. BMC Bioinformatics 2015 16 (Suppl 1), S7.
8. CW Lee, HJ Wang, JK Hwang, CP Tseng Protein Thermal Stability Enhancement by Designing Salt Bridges: A Combined Computational and Experimental Study PloS one 2014 9 (11), e112751
9. Huang TT, del Valle Marcos ML, Hwang JK, Echave J. A mechanistic stress model of protein evolution accounts for site-specific evolutionary rates and their relationship with packing density and flexibility. J. BMC Evol Biol. 2014 Apr 9;14:78. doi: 10.1186/1471-2148-14-78.
10. Yeh SW, Liu JW, Yu SH, Shih CH, Hwang JK, Echave J. Site-specific structural constraints on protein sequence evolutionary divergence: local packing density versus solvent exposure. Mol Biol Evol. 2014 Jan;31(1):135-9. doi: 10.1093/molbev/mst178.
11. Yeh SW, Huang TT, Liu JW, Yu SH, Shih CH, Hwang JK, Echave J. Local packing density is the main structural determinant of the rate if protein sequence sequence at the site level. J. Biomed Res Int. 2014;2014:572409. doi: 10.1155/2014/572409.
12. Yu CS, Cheng CW, Su WC, Chang KC, Huang SW, Hwang JK, Lu CH. CELLO2GO: a web server for protein subCELlular LOcalization prediction with functional gene ontology annotation. PLoS One. 2014 Jun 9; 9(6):e99368. doi: 10.1371/journal.pone.0099368
13. Lee CH, Chen YW, Huang YT, Pan YJ, Lee CH, Lin SM, Huang LK, Lo YY, Huang YF, Hsu YD, Yen SC, Hwang JK, Pan RL. Functional investigation of transmembrane helix 3 in H⁺-translocating pyrophosphatase. J Membr Biol. 2013 Dec; 246(12):959-66.
14. Chang CM, Huang YW, Shih CH, Hwang JK. On the relationship between the sequence conservation and the packing density profiles of the protein complexes. Proteins. 2013 Jul;81(7):1192-9. doi: 10.1002/prot.24268.
15. Chen CC, Er TK, Liu YY, Hwang JK, Barrio MJ, Rodrigo M, Garcia-Toro E, Herreros-Villanueva M. Computational Analysis of KRAS mutations: Implications for different effects on the KRAS p.G12D and p.G13D mutations. Plos ONE 2013 . 2013;8(2):e55793. doi: 10.1371/journal.pone.0055793.
16. Liu YY, Shih CH, Hwang JK, Chen CC. Deriving correlated motions in proteins from x-ray structure refinement using TLS parameters Gene 2013 Apr 10;518(1):52-8. doi: 10.1016/j. gene.2012.11.086.
17. Shih CH, Chang CM, Lin YS, Lo WC, Hwang JK. Evolutionary information hidden in a single protein structure. Proteins (2012) 80, 16472.
18. Lai YL, Chen CC, Hwang JK. pKNOT v2.0: the protein KNOT web server. Nucleic Acids Research (2012) doi: 10.1093/nar/gks592
19. Lo WC, Wang LF, Liu YY, Dai T, Hwang JK Lyu PC. CPred: a web server for predicting viable circular permutations in proteins. Nucleic Acids Research (2012) 10.1093/nar/gks529.
20. Lo WC, Dai T, Liu YY, Wang LF, Hwang JK, PC Lyu. Deciphering the preference and predicting the viability of circular permutations in proteins. (2012) Plus One, 7, e31791.
21. Chien YT, Hwang JK, Huang SW. On the relationship between residue solvent exposure and thermal fluctuations in proteins. Protein Structure (2012) ISBN 979-953-307-576-0.
22. Er TK, Chen CC, Liu YY, Chang LC, Chien, YH, Chang JG, Hwang JK Jong YJ. Computational analysis of a novel mutation in ETFDH gene highlights in its long-range effects on the FAD-binding motif. BMC Structural Bioinformartics (2011) 11:43.
23. Huang SW, Yu SH, Shih CH, Guan HW, Huang TT, Hwang JK. On the relationship between catalytic residues and their protein contact number. Current Protein and Peptide Science (2011) 1;12(6):574-9.
24. Chiang AS, Lin CY, Chuang CC, Chang HM, Hsieh CH, Yeh CW, Shih CT, Wu JJ, Wang GT, Chen YC, Wu CC, Chen GY, Ching YT, Lee PC, Lin CY, Lin HH, Wu CC, Hsu HW, Huang YA, Chen JY, Chiang HJ, Lu CF, Ni RF, Yeh CY, Hwang JK. Three-Dimensional Reconstruction of Brain-wide Wiring Networks in Drosophila at Single-Cell Resolution. Curr Biol. (2011) Jan 11;21(1):1-11.
25. Huang SW, Hwang JK. Bioinformatics-Experimantal Biology Systems: On the Structural Characteristics of the Protein Active Sites and Their Relation to Thermal Fluctuations (2011). ISBN: ISBN 978-953-307-280-7.
26. Chu CH, Lo WC, Wang HW, Hsu YC, Hwang JK, Lyu PC, TW Pai, CY Tang. Detection and alignment of 3D domain swapping proteins using angle-distance image-based secondary structural matching techniques. Plos One (2010) 14;5(10):e13361.
27. *Lai et al. Comprehensive Analysis of Knotted Proteins in Sequence and Genome Analysis: Methods and Applications (2010). ISBN: 978-0-9807330-4-4
28. Chen CC, Hwang JK, Yang JM PS2-v2: template-based protein structure prediction server. BMC Bioinformatics (2009) 10, 366
29. Huang SW, Shih CH, Lin CP, Hwang JK Prediction of NMR order parameters in proteins using weighted protein contact-number model. Theor Chem Acc (2008) 121, 197-200
30. Cheng SW, Su ECY, Hwang JK, Sun TY, Hsu WL Predicting RNA-binding sites of proteins using support vector machines and evolutionary information. BMC Bioinformatics, (2008) 9, S6.
31. Lin CP, Huang SW, Lai YL, Yen SC, Shih CH, Lu CH, Huang CC, Hwang JK. Deriving protein dynamical properties from weighted protein contact number, Proteins: Structure, Function and Bioinformatics (2008) 72, 929-935.
32. Lu CH, Huang SW, Lai YL, Lin CP, Shih CH, Huang CC, Hsu WL, Hwang JK. On the relationship between the protein structure and protein dynamics, Proteins: Structure, Function and Bioinformatics (2008) 72, 625-634
33. Shih CH, Huang SW, Yen SC, Lai YL, Yu SH, Hwang JK. Computation of protein dynamics without a mechanical model, Proteins: Structure, Function and Bioinformatics (2007) 68, 34-38
34. Chiu, YY, Hwang JK, Yang JM, Soft energy function and generic evolutionary method for discriminating native from non-native protein conformations, J. Comp. Chem. (2008) 29, 1364-1373.
35. Tsai YC, Lin YM, Hwang JK, Yu JSK, On the Stereochemistry of Zn-Zn Bonds: Synthesis, Structural Transformation, and Computations, Chem. Comm. (2007) 40:4125-4127
36. Su ECY, Chiu HS, Lo A, Hwang JK, TY Sung, WL Hsu, Protein subcellular localization prediction based on compartment-specific features and structure conservation, BMC Bioinformatics (2007) 8:330-341.
37. Lai YL, Yen SC, Yu SH, Hwang JK. pKNOT: the Protein KNOT web server, Nucleic Acids Research (2007) 35:W420-W424 ; [Go to: The pKNOT server].
38. Wong YH, Lee TY, Liang HK, Huang CM, Yang YH, Chu CH, Huang HD, Ko MT, Hwang JK, KinasePhos 2.0: a web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns, Nucleic Acids Research (2007) 35:W588-594.
39. Huang CL, Liu JH, Chiu WC, Huang SW, Hwang JK, Wang WC. Crystal structure of Helicobacter pylori formamidase AmiF reveals a cysteine-glutamate-lysine catalytic triad. J. Biol. Chem. (2007) 282:12220-12229.
40. Lin YS, Hsu WL, Hwang JK, Li WH. Proportion of solvent-exposed amino acids in a protein and rate of protein evolution, Molecular Biology and Evolution (2007) 24, 1005-11.
41. Lu CH, Chen YC, Yu CS, Hwang JK. Predicting disulfide connectivity patterns, Proteins: Structure, Function and Bioinformatics (2007) 67: 262-270
42. Tsai YC, Lin YM, Yu, JSK, Hwang JK. A three-coordinate and quaruply bonded Mo-Mo-Complex, J. Am. Chem. Soc. (2006) 128:13980-13981
43. Lin YS, Byrnes JK, Hwang JK, Li WH. Codon usage bias versus gene conversion in the evolution of yeast duplicate genes. Proc. Natl. Acad. Sci. USA. (2006) 103:14412-1441628.
44. Lin YS, Hwang JK, Li WH. Protein complexity, gene duplicability and gene dispensability in the yeast genome. Gene. (2006) [Epub ahead of print].
45. *Yu CH, Chen YC, Lu CH, Hwang JK. Prediction of protein subcellular localization. Proteins: Structure, Function and Bioinformatics (2006), 387, 109-117.
46. Chiu WC, You JY, Liu JS, Hsu SK, Hsu WH, Shih CH, Hwang JK, Wang WC, Structure-stability-activity relationship in covalently c 1 ross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase. J. Mol. Biol. (2006), 359: 741-753.
47. Chen CC, Hwang JK, JM Yang. Protein structure prediction server. Nucleic Acids Research (2006), 34: W152-157.
48. Lu CH, Lin SH, Chen YC, Yu CS, Chang SY, Hwang JK. The fragment transformation method to detect the protein structural motifs. Proteins: Structure, Function and Bioinformatics (2006), 63:636-643.
49. Hung SW, Hwang JK, Tseng F, Chang JM Chen CC, Chieng CC. Molecular dynamics simulation on enhancement of CTX and E6 protein binding on mixed SAMs molecules. Nanotechnology (2006), 17, S8-13
50. Chen YC, Hwang JK Prediction of disulfide connectivity from protein sequences. Proteins: Structure, Function and Bioinformatics (2005) 61, 507-512.
51. Huang SW, Hwang JK. Computation of conformational entropy from protein sequences using the machine-learning method - Application to the study of the relationship between structural conservation and local structural stability. Proteins: Structure, Function and Bioinformatics (2005), 59, 802-809.
52. Liang HK, Huang CM, Ko MT, Hwang JK. The Amino Acid-Coupling Patterns in Thermophilic Proteins. Proteins: Structure, Function and Bioinformatics (2005), 59, 58-63.
53. Lin YS, Tzeng CS, Hwang JK. Reassessment of morphological characters in freshwater eels (genus Anguilla, Anguillidae) shows congruence with molecular phylogeny estimate. Zoologica Scripta (2005), 34, 225-234.
54. Chan CH, Liang HK, Hsiao NW, Ko MT, Lyu PC, Hwang JK. The relationship between local structural entropy and protein thermostability. Proteins: Structure, Function and Bioinformatics (2004), 57, 684-691.).
55. Chen YC, Lin YS, Lin CJ and Hwang JK. Prediction of the Bonding States of Cysteines using the Support Vector Machines Based on Multiple Feature Vectors and Cysteine State Sequences. Proteins: Structure, Function and Bioinformatics (2004), 55, 1046-42.
56. Yu CS, Lin CJ, Hwang JK, Predicting Subcellular Localization of Proteins For Gram-Negative Bacteria by Support Vector Machines Based on n-Peptide Compositions. Protein Science (2004), 13, 1402-1406
57. Yu JSK, Hwang JK, Tang CY, Yu CH. Numerical performance and throughput benchmark for electronic structure calculations in PC-Linux System with new architectures, updated compilers and library. J. Chem. Inf. Comput. Sci (2004), 44, 635-642.
58. Yu CS, Wang JY, Yang JM, Lyu PC, Lin CJ, Hwang JK, Fine-grained protein fold assignment by support vector machines using generalized n-peptide coding schemes and jury voting from multiple parameter sets. Proteins: Structure, Function, Genetics (2003) 50,531-536
59. Horng JT, Huang HD, Wang SH, Chen MY, and Hwang JK, Computing motif correlations in proteins. J. Comp. Chem. (2003), 24, 2032-2043.
60. Chuang CC, Chen CY, Yang JM, Lyu PC, Hwang JK, Relationship between protein structures and disulfide-bonding patterns. Proteins: Structure, Function and Genetics (2003), 53, 1-5.
61. Chan CH, Lyu PC, Hwang JK, Computation of the Protein Structure Entropy and its Applications to Protein Folding Processes. J. Chin. Chem. Soc. (2003), 50, 677-684.
62. Yang JM, Tsai CH, Hwang MJ, Tsai HK, Hwang JK, Kao CY, GEM: A Gaussian evolutionary method for predicting protein side-chain conformations. Protein Sci. (2002), 11, 1897-1907.
63. Hwang JK,The partial averaging Fourier path integral approach based on the harmonic reference path, Theo. Chem. Acc. 101 (1999) 5, 359-363
64. Lin CH, Chan FCH, Hwang JK, Lyu PC, Calcium binding mode of g-carboxyglutamic acids in Conantokins, Protein Engineering (1999) 12, 101-107
65. Fan ZZ, Hwang JK, Warshel A, Using simplified protein representaion as a reference potential for all-atom calculations of folding free energy Theo. Chem. Acc. (1999) 103, 77-80
66. Yang YS, Pan JJ, Hwang JK, Probing phenol binding environment of sulfotransferase. Protein Engineering 10A, 70 (1997)
67. Vyas A, Pan JJ, Patel HV, Vyas KA, Chiang CM, Sheu YC, Hwang JK, Wu WG, Analysis of binding of cobra cardiotoxins to heparin reveals a new beta-sheet heparin-binding structural motif. J. Biol. Chem. 272, 9661(1997)
68. Hwang JK, Warshel A, On the relationship between the dispersed polaron and spin-boson models. Chem. Phys. Lett. 271, 223 (1997).
69. Chan FCH, Pan JJ, Fan ZZ, Hsieh FMJ, Hwang JK, Computer simulation of chemical reactions in biological systems, Chemistry, 55, 1 (1997)
70. Pan JJ, Hwang JK, Mixed Quantum Mechanical/Molecular Mechanical Simulations of Chemical Reactions in Solution and in Enzymes, in Pacific Symposium on Biocomputing '96 edited by Lawrence Hunter and Teri E. Klein. (World Scientific, Singapore, 1996) p.539-549
71. Hwang JK, Pan JJ, Classical Trajectory Mapping Approach for Simulations of Chemical Reactions in solution and in enzyme. J. Phys. Chem. 100, 909 (1996).
72. Hwang JK, Warshel A, How important are quantum mechanical nuclear motions in enzyme catalysis. J. Am. Chem. Soc. 118, 11745 (1996)
73. Hwang JK, Liao WF, Side-chain Prediction by Neural Networks and Simulated Annealing Optimization. Prot. Eng. 8, 363-370 (1995)
>> My first attempt in using machine learning method to predict side-chain orientations of proteins.
74. Hwang JK, Pan JJ, Simulation of Chemical Reactions in Solution by a Combination of Classical and Quantum Mechanical Approach. Chem. Phys. Lett. 243, 171-175 (1995)
75. Hwang JK, Chang CC, Computer Simulation of Enzymatic Reaction Chemistry, 52, 246-250 (1994).
76. Hwang JK, Warshel A, A Quantized Classical Path Approach for Calculations of Quantum Mechanical Rate Constants. J. Phys. Chem. 97, 10053-10058 (1993).
77. Warshel A, Hwang JK, Åqvist J, Computer Simulations of Enzymatic reactions: Examination of Linear Free-Energy Relationships and Quantum-mechanical Corrections in the Initial Proton-Transfer Step of Carbonic Anhydrase. Faraday Discuss. 93, 225-238 (1992).
78. Hwang JK, Chu ZT, Yadav A, Warshel A, Simulations of Quantum Mechanical Corrections for Rate Constants of Hydride-transfer Reactions in Enzymes and Solutions. J. Phys. Chem. 95 8445(1991).
79. Warshel A, Naray-Szabo G, Sussman F, Hwang JK, Perspectives in Biochemistry Vol II, edited by Hans Neurath, (American Chemical Society 1991), p. 115.
80. Warshel A, Chu ZT, Hwang JK, The Dynamics of the Primary event in rhodopsins revisted. Chem. Phys. 158, 303 (1991)
81. Warshel A, Naray-Szabo G, Sussman F, Hwang JK, How Do Serine Proteases Really Work? Biochemistry 28, 3629 (1989).
82. Hwang JK, Calculation of quantum mechanical free energy at low temperature. Theo. Chem. Acc. 98, 202 (1998)
83. Hwang JK and Warshel A, Why Ion Pair Reversal by Protein Engineering is Unlikely to Succeed. Nature, 334, 270 (1988).
84.Warshel A, Sussman F, Hwang JK, Evaluation of Catalytic Free Energies in Genetically Modified Proteins. J. Mol. Biol. 201, 139 (1988).
85. Creighton S, Hwang JK, Warshel A, Parson WW, Norris J, Simulating The Dynamics of the Primary Charge Separation Process in Bacterial Photosynthesis. Biochemistry 27 774 (1988).
86. Hwang JK, Sussman F, and Warshel A, Simulating the Energetics and Dynamics of Enzymatic Reactions in Genetically Modified Enzymes in Structure and Expression, edited by R.H Sarma and M.H. Sarma (Adenine Press,New York 1988), p. 95.
87. Hwang JK, Creighton S, King G, Whitney D, and Warshel A, Effects of Solute-Solvent Coupling and Solvent Saturation on Solvation Dynamics of Charge Transfer Reactions. J. Chem. Phys. 89, 859 (1988).
88. Hwang JK, King G, Creighton S, Warshel A, Simulation of Free Energy Relationships and Dynamics of SN2 Reactions in Aqueous Solutions. J. Am. Chem. Soc. 110, 5297 (1988).
89. Hwang JK, Warshel A, Semiquantitative Calculations of Catalytic Free energies in Genetically Modified Subtilisin. Biochemistry, 26, 2669 (1987).
90. Hwang JK, Warshel A, Microscopic Examination of Free-Energy Relationships for Electron Transfer in Polar Solvents. J. Am. Chem. Soc. 109, 715 (1987).
91. Warshel A, Hwang JK, Simulation of the Dynamics of Electron Transfer Reactions in Polar Solvents: Semiclassical Trajectories and Dispersed Polaron Approaches. J. Chem. Phys. 84, 4938 (1986).
92. Hwang JK, Warshel A, Semiclassical Simulation of the Spectra of Anharmonic Molecules: Problems and Alternatives. Chem. Phys. Lett. 115, 182 (1985).
93. Hwang JK, Warshel A, A Shortcut for Multidimensional Quantization. The Average Partial Action Method. Chem. Phys. Lett. 118, 289 (1985).
94. Warshel A, Hwang JK, Quantized Semiclassical Trajectory Approach for Evaluation of Vibronic Transitions in Anharmonic Molecules. J. Chem. Phys.1756, 82 (1985).
95. Hwang JK, Yen GC, Hwang LS, Detection of Vegetable Oil Adulteration by HPLC Analysis of Triglycerides. J. Chin. Agric. Chem. Soc. 91, 20 (1982).
- Academic Publications
PhD (Computer Science and Information Engineering, National Central University, Taiwan)
Bioinformatics, Genomics, Metagenomics & Microbiome, Intelligent Biomedical Technologies (Drug Development, Genetic Test, & Precision Medicine), AI & Machine Learning, Biological Database Design & Development
Personal Website: Link
Prof. Hsien-Da Huang is a professor at the School of Life and Health Sciences & Arieh Warshel Institute of Computational Biology, The Chinese University of Hong Kong, Shenzhen. He received PhD at Department of Computer Science and Information Engineering, National Central University, Taiwan, in 2003. He was a chair professor and vice dean at the College of Biological Science and Technology, National Chiao Tung University, Taiwan. During 2009-2016, he was the Chairman at Department of Biological Science and Technology, NCTU. He was the President of Taiwan Society of Bioinformatics and Systems Biology (2014-2017).
Prof. Huang’s group majorly focuses on biological multi-disciplinary research topics, including Bioinformatics, Genomics, Metagenomics & Microbiome, Intelligent Biomedical Technologies (Drug Development, Genetic Test, & Precision Medicine), AI & Machine Learning, and Biological Database Design & Development. During last ten years, He published more than 130 peer-reviewed publications, mostly in prestigious journals, including Science, Molecular Cell, Circulation, The Journal of Clinical Investigation, PLoS Biology, Hepatology, Cancer Research, and Nucleic Acids Research. If using several popular measures to assess the impacts of Prof. Huang’s research, he receives 13 highly-cited papers, more than 40 papers with 10.0 or higher impact factor, H-index as 41, more than 6000 citations in Web of Science and more than 9800 citations in Google Scholar.
Prof. Huang’s group developed a microRNA database, miRTarBase, which is an internationally recognized repository for collecting experimental miRNA-Target interaction (MTI). The users are majorly from the United States, China, Japan, Germany, and the UK. The database is continuously maintained and now broadly utilized and referred in life science and medical research field.
Prof. Huang received Outstanding Research Award (2010 and 2015) and Ta-You Wu Memorial Award (2009) of Ministry of Science and Technology, Taiwan.
Selected Journal Publications (* corresponding author):
- MethHC 2.0: information repository of DNA methylation and gene expression in human cancer. (2021) Nucleic Acids Research, Vol. 49, pp. D1268-D1275.
- miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. (2020) Nucleic Acids Res., Vol. 48, D1, pp. D148-D154. (SCI, highly-cited paper)
- miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. (2018) Nucleic Acids Res., Vol. 46, D1, pp. D296-D302. (SCI, highly-cited paper)
- Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes. (2018) Science, Vol. 360, No. 6393, pp. 1126-1129.
- MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma. (2018) Scientific Report, Vol.8, No.1, pp.12284.
- Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops. (2018) Int. J. Mol. Sci., Vol. 19, No.8, pp. E2335.
- Ouroboros resembling competitive endogenous loop (ORCEL) in circular RNAs revealed through transcriptome sequencing dataset analysis. (2018) BMC Genomics, Vol.19 (Suppl. 2), pp.171.
- MicroRNA-92a Mediates Endothelial Dysfunction in CKD. (2017) J. Am Soc. Nephrology, Vol. 28, No. 11, pp. 3251-3261.
- α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. (2017) Nature Immunology, Vol. 18, No. 9, pp. 985-994.
- Bidirectional cross-kingdom RNAi and fungal uptake of external RNAs confer plant protection. (2016) Nature Plants, Vol. 2, pp. 16151. (SCI, highly-cited paper)
- Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility. (2017) Circulation, Vol. 136, No. 14, pp. 1315-1330.
- dbPTM 2016: 10-year anniversary of a resource for post-translational modification of proteins. (2016) Nucleic Acids Research, Vol. 44, D1, pp. D435-46.
- miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. (2016) Nucleic Acids Research, Vol. 44, D1, pp. D239-47. (SCI, highly-cited paper)
- PlantPAN 2.0: an update of plant promoter analysis navigator for reconstructing transcriptional regulatory networks in plants. (2016) Nucleic Acids Research, Vol. 44, D1, pp. D1154-60.
- CircNet: a database of circular RNAs derived from transcriptome sequencing data. (2016) Nucleic Acids Research, Vol. 44, D1, pp. D209-15. (SCI, highly-cited paper)
- MethHC: a database of DNA methylation and gene expression in human cancer. (2015) Nucleic Acids Research, Vol. 43 (Database issue), pp. D856-61.
- Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. (2015) Circulation, Vol. 131, No. 9, pp. 805-14.
- The effects of actin cytoskeleton perturbation on keratin intermediate filament formation in mesenchymal stem/stromal cells. (2014) Biomaterials, Vol. 35, No. 13, pp. 3934-44.
- miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions. (2014) Nucleic Acids Research, Vol. 42, pp. D78-85. (SCI, highly-cited paper)
- COL11A1 Promotes Tumor Progression, and Predicts Poor Clinical Outcome in Ovarian Cancer. (2013) Oncogene, Vol. 33, No. 26, pp. 3432-40.
- Transcribed pseudogene ψPPM1K generates endogenous siRNA to suppress oncogenic cell growth in hepatocellular carcinoma. (2013) Nucleic Acids Research, Vol. 41, No. 6, pp. 3734-47.
- Sterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibility. (2013) Circulation, Vol. 128, No. 6, pp. 632-42.
- Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis. (2013) Journal of Clinical Investigation, Vol. 123, No. 3, pp. 1057-67.
- Fungal small RNAs as novel effectors to suppress plant immunity by hijacking the host RNAi machinery. Science, Vol. 342, No. 6154, pp. 118-123. (SCI, highly-cited paper)
- MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. (2012) Journal of Clinical Investigation, Vol. 122, No. 8, pp. 2884-97. (SCI, highly-cited paper)
- Let-7b is a novel regulator of hepatitis C virus replication. (2012) Cellular and Molecular Life Sciences, Vol. 69, No. 15, pp. 2621-33.
- Clusters of nucleotide substitutions and insertion/deletion mutations are associated with repeat sequences. (2011) PLoS Biology, Vol. 9, No. 6, e1000622.
- RegPhos: a system to explore the protein kinase-substrate phosphorylation network in humans. (2011) Nucleic Acids Research, Vol.39, pp. D777-87.
- miRTarBase: a database curates experimentally validated microRNA-target interactions. (2011) Nucleic Acids Research, Vol.39, pp. D163-9. (SCI, highly-cited paper)
- miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. (2012) Cancer Research, Vol. 72, No. 14, pp. 3631-41. (SCI, highly-cited paper)
- Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data. (2011) Nucleic Acids Research, Vol. 39, No. 21, pp.9345-9356.
- Arabidopsis Argonaute 2 Regulates Innate Immunity via miRNA393*-Mediated Silencing of a Golgi-Localized SNARE Gene, MEMB12. (2011) Molecular Cell, Vo. 42, No. 3, pp. 356-366.
- Flow-regulation of Krüppel-like Factor 2 Is Mediated by MicroRNA-92a (2011) Circulation, Vol. 124, No. 5, pp. 633-41.
- MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. (2009) Hepatology, Vol. 49, No. 5, pp. 1571-82. (SCI, highly-cited paper)
- Academic Publications
PhD (Bioinformatics, National Chiao Tung University, Taiwan)
BS (Computer Science and Information Engineering, National Central University, Taiwan)
Bioinformatics, Genomics and Proteomics, Network Biology, Data Mining in Omics Science, Shallow and Deep Learning, Database Design and Software Development.
Personal Website: Link
Dr. Tzong-Yi Lee received the B.S. degree in Computer Science and Information Engineering from National Central University (NCU), Taiwan and the Ph.D. degree in Bioinformatics from National Chiao Tung University (NCTU), Taiwan, in 2002 and 2008, respectively. From 2009 to 2017, Dr. Lee was an Assistant Professor, Associate Professor (2012), and Professor (2015) with the Department of Computer Science and Engineering, Yuan Ze University, Taiwan. Currently he is an Associate Professor in the School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, China. Dr. Lee’s research interests include bioinformatics, genomics and proteomics, network biology, data mining in Omics science, shallow and deep learning, database design and software development. His research team currently specialize in gene promoters and transcriptional regulations, circular RNA regulation, microbiota and functional analyses, protein post-translational modifications (PTMs), protein kinases and signaling pathway, protein ubiquitylation and E3 ligases regulations, protein glycosylation and glycosyl-structure identification, antimicrobial peptides (AMPs), multidrug-resistant pathogens diagnosis, and drug repurposing. His longer-term research goals are focusing on the integration of Bioinformatics and Omics science to address emerging biological and clinical questions for precision medicine.
Dr. Lee have published over 70 articles in SCI journals, including Nucleic Acids Research, Bioinformatics, Briefings in Bioinformatics, Journal of Proteome Research, DATABASE: The Journal of Biological Databases and Curation, BMC Genomics, PLoS ONE, IEEE/ACM Transactions on Computational Biology and Bioinformatics, etc. His research achievements have awarded him with Yuan Ze University Young Scholar Research Award (2011), Yuan Ze University Outstanding Research Award (2012 and 2016), and the Y. Z. Hsu Outstanding Professor Award (2015). Additionally, he is one of the Editorial Board of Genomics, Proteomics, and Bioinformatics (GPB), Proteomics & Bioinformatics: Current Research, International Journal of Bioinformatics & Biological Systems (IJBBS), and Informatics since 2015.
Selected Journal Publications (* corresponding author):
1. Hui-Ju Kao, Kai-Yao Huang and Tzong-Yi Lee*, 2018, “Exploiting Deep Learning Method to Identify Succinylated Sites on Lysine Residues”, Bioinformatics, accepted.
2. Hsin-Yao Wang‡, Tzong-Yi Lee‡ (‡ joint first authorship), Yi-Ju Tseng, Tsui-Ping Liu, Kai-Yao Huang, YungTa Chang, Chun-Hsien Chen*, Jang-Jih Lu*, March 2018, "A new scheme for strain typing of methicillin-resistant Staphylococcus aureus on the basis of matrix-assisted laser desorption ionization time-of-flight mass spectrometry by using machine learning approach," PLoS ONE, 13(3): e0194289.
3. Kai-Yao Huang, Tzu-Hao Chang, Jhih-Hua Jhong, Yu-Hsiang Chi, Wen-Chi Li, Chien-Lung Chan, K. Robert Lai and Tzong-Yi Lee*, 2017, "Identification of natural antimicrobial peptides from bacteria through metagenomic and metatranscriptomic analysis of high-throughput transcriptome data of Taiwanese oolong teas," BMC Systems Biology, Vol. 11 (Suppl 7):131.
4. Shun-Long Weng†, Kai-Yao Huang† († joint first authorship), Julia Tzu-Ya Weng, Fang-Yu Hung, Tzu-Hao Chang* and Tzong-Yi Lee*, 2017, “Genome-wide discovery of viral microRNAs based on phylogenetic analysis and structural evolution of various human papillomavirus subtypes,” Briefings in Bioinformatics, 2017 bbx046. doi: 10.1093/bib/bbx046.
5. Van-Nui Nguyen, Kai-Yao Huang, Chien-Hsun Huang, K. Robert Lai* and Tzong-Yi Lee*, 2017, "A new scheme to characterize and identify protein ubiquitination sites," IEEE/ACM Transactions on Computational Biology and Bioinformatics, Vol. 14(2):393-403.
6. Kai-Yao Huang, Min-Gang Su, Hui-Ju Kao, Yun-Chung Hsieh, Jhih-Hua Jhong, Kuang-Hao Cheng, Hsien-Da Huang, Tzong-Yi Lee*, 2016, "dbPTM 2016: ten-year anniversary of a resource of post-translational modification of proteins," Nucleic Acids Research 2016 Jan. 4, Vol. 44(D1):D435-D446.
7. Chi-Nga Chow, Han-Qin Zheng, Nai-Yun Wu, Chia-Hung Chien, Hsien-Da Huang, Tzong-Yi Lee, Yi-Fan Chian-Hsieh, Ping-Fu Hou, Tien-Yi Yang, and Wen-Chi Chang*, 2016, "PlantPAN 2.0: an update of Plant Promoter Analysis Navigator for reconstructing transcriptional regulatory networks in plants," Nucleic Acids Research 2016 Jan. 4; Vol. 44(D1):D1154-D1160.
8. Van-Nui Nguyen, Kai-Yao Huang, Julia Tzu-Ya Weng, K. Robert Lai* and Tzong-Yi Lee*, 2016, "UbiNet: an online resource for exploring functional associations and regulatory networks of protein ubiquitylation," DATABASE: The Journal of Biological Databases and Curation, 2016 Apr 25;2016. pii: baw054.
9. Van-Minh Bui, Cheng-Tsung Lu, Thi-Trang Ho, and Tzong-Yi Lee*, 2016, "MDD-SOH: Exploiting maximal dependence decomposition to identify S-sulfenylation sites with substrate motifs" Bioinformatics, 2016 Jan 15, 32(2):165-72.
10. Yi-Ju Chen, Cheng-Tsung Lu, Min-Gang Su, Kai-Yao Huang, Wei-Chieh Ching, Hsiao-Hsiang Yang, Yen-Chen Liao, Yu-Ju Chen* and Tzong-Yi Lee*, 2015, "dbSNO 2.0: a resource for exploring structural environment, functional and disease associations, and regulatory networks of protein S-nitrosylation" Nucleic Acids Research Vol. 43 (D1): D503-11.
11. Yi-Ju Chen, Cheng-Tsung Lu, Tzong-Yi Lee* and Yu-Ju Chen*, 2014, "dbGSH: a database of S-Glutathionylation" Bioinformatics, 2014 Aug 15;30(16):2386-8.
12. Kai-Yao Huang, Hsin-Yi Wu, Yi-Ju Chen, Cheng-Tsung Lu, Min-Gang Su, Yun-Chung Hsieh, Chih-Ming Tsai, Kuo-I Lin, Hsien-Da Huang, Tzong-Yi Lee* and Yu-Ju Chen*, 2014, "RegPhos 2.0: an updated resource to explore protein kinase-substrate phosphorylation networks in mammals," DATABASE: The Journal of Biological Databases and Curation, 2014(0): bau034.
13. Min-Gang Su, Kai-Yao Huang, Cheng-Tsung Lu, Hui-Ju Kao, Ya-Han Chang and Tzong-Yi Lee*, 2014, "topPTM: a new module of dbPTM for identifying functional post-translational modifications in transmembrane proteins," Nucleic Acids Research, Vol. 42 (D1): D537-D545.
14. Cheng-Tsung Lu, Kai-Yao Huang, Min-Gang Su, Tzong-Yi Lee*, Neil Arvin Bretaña, Wen-Chi Chang, Yi-Ju Chen, Yu-Ju Chen and Hsien-Da Huang*, 2013, "dbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications," Nucleic Acids Research, 41 (D1):D295-305.
15. Tzong-Yi Lee*, Yi-Ju Chen, Cheng-Tsung Lu, Wei-Chieh Ching, Yu-Chuan Teng, Hsien-Da Huang and Yu-Ju Chen*, 2012, "dbSNO: a database of cysteine S-Nitrosylation," Bioinformatics, 28(17):2293-5.
16. Tzong-Yi Lee*, Wen-Chi Chang*, Justin BK Hsu, Tzu-Hao Chang and Dray-Ming Shien, 2012, January "GPMiner: an integrated system for mining combinatorial cis-regulatory elements in mammalian gene group," BMC Genomics, 13(Suppl 1):S3.
17. C.H. Chien, Y.M. Sun, W.C. Chang, P.Y. Chiang-Hsieh, Tzong-Yi Lee, W.C. Tsai, J.T. Horng, A.P. Tsou*, H.D. Huang*, 2011, "Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data," Nucleic Acids Research, 39(21):9345-9356.
18. Tzong-Yi Lee*, Zong-Qing Lin, Sheng-Jen Hsieh, Neil Arvin Bretaña, and Cheng-Tsung Lu, 2011, "Exploiting maximal dependence decomposition to identify conserved motifs from a group of aligned signal sequences," Bioinformatics, 27(13): 1780-1787.
19. Shu-An Chen, Yu-Yen Ou, Tzong-Yi Lee and M. Michael Gromiha*, 2011, June "Prediction of transporter targets using efficient RBF networks with PSSM profiles and biochemical properties," Bioinformatics, 27(15):2062-7.
20. Tzong-Yi Lee, Justin Bo-Kai Hsu, Wen-Chi Chang, and Hsien-Da Huang* , 2011, "RegPhos: a system to explore the protein kinase-substrate phosphorylation network in humans," Nucleic Acids Research, Vol. 39, D777-D787.
21. Dray-Ming Shien†, Tzong-Yi Lee† († joint first authorship), Wen-Chi Chang, Justin B.K. Hsu, Jorng-Tzong Horng, Po-Chian Hsu, Ting-Yuan Wang and Hsien-Da Huang*, 2010, "Incorporating Structural Characteristics for Identification of Protein Methylation Sites," Journal of Computational Chemistry, Vol. 30, No. 9, pp.1532-1543.
22. Tzong-Yi Lee, Justin Bo-Kai Hsu, Feng-Mao Lin, Wen-Chi Chang, Po-Chiang Hsu, and Hsien-Da Huang, 2010, "N-Ace: using solvent accessibility and physicochemical properties to identify protein N-Acetylation sites," Journal of Computational Chemistry, Vol. 31 (15), 2759-2771. (Cover Story)
23. W.C. Chang†, Tzong-Yi Lee† († joint first authorship), D.M. Shien, J. B.K. Hsu, P.C. Hsu, T.Y. Wang, J.T. Horng, H.D. Huang* and R.L. Pan*, 2009, Nov 30 "Incorporating support vector machine for identifying protein tyrosine sulfation sites," Journal of Computational Chemistry, 2009 Nov 30; 30(15):2526-37.
24. W.C. Chang, Tzong-Yi Lee, H.D. Huang*, H.Y. Huang, R.L. Pan*, 2008, "PlantPAN: Plant Promoter Analysis Navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene group," BMC Genomics, 9:561.
25. Y.H. Wong†, Tzong-Yi Lee† († joint first authorship), H.K. Liang, C.M. Huang, Y.H. Yang, C.H. Chu, H.D. Huang* , M.T. Ko, and J.K. Hwang, 2007, "KinasePhos 2.0: a web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns," Nucleic Acids Research, Vol 35, W588-594.
26. Tzong-Yi Lee, J.T. Horng, H.F. Juan, H.D. Huang, L.C. Wu, and F.M. Lin, 2006, "An agent-based system to discover protein-protein interactions, identify protein complexes and proteins with multiple peptide mass fingerprints," Journal of Computational Chemistry, Vol. 27, No. 9, 1020-32.
27. Tzong-Yi Lee, H.D. Huang*, J.H. Hung, Y.S. Yang, and T.H. Wang*, 2006, "dbPTM: An information repository of protein post-translational modification," Nucleic Acids Research, Vol. 34, D622-D627.
28. J.H. Hung†, H.D. Huang†,* († joint first authorship), and Tzong-Yi Lee, "ProKware: an integrated software for presenting protein structural properties in protein tertiary structures," Nucleic Acids Research, Vol 34, W89-W94.
29. H.D. Huang, Tzong-Yi Lee, L.C. Wu, F.M. Lin, J.T. Horng, and A.P. Tsou, 2005, "MultiProtIdent: identifying proteins using database search and protein-protein interactions," Journal of Proteome Research, Vol. 4(3), 690-697.
30. H.D. Huang*, Tzong-Yi Lee, S.W. Tseng, and J.T. Horng, 2005, "KinasePhos: a web tool for identifying protein kinase-specific phosphorylation sites," Nucleic Acids Research, Vol. 33, W226-229.
- Academic Publications
PhD (The University of Tokyo)
MEng (Kyoto University)
BEng (Kyoto University)
Computational chemistry, Computational Biology
Prof. HIRAO, Hajime obtained his BEng and MEng degrees from Kyoto University in 1998 and 2000, respectively, and his PhD from The University of Tokyo in 2004. He did his postdoctoral studies at The Hebrew University of Jerusalem, Emory University, and Kyoto University. Since his student days, he has been engaged in computational chemistry research at various institutions such as Novartis, Nanyang Technological University, and City University of Hong Kong. His research group is interested in computationally deriving general principles of chemical reactions and molecular interactions occurring in nature and labs, and also in rationally designing therapeutic and other types of functional molecules with experimentalists.
1. Liu, C.-Y.; Chen, X.-R.; Chen, H.-X.; Niu, Z.; Hirao, H.; Braunstein, P.; Lang, J.-P. "Ultrafast Luminescent Light-Up Guest Detection Based on the Lock of the Host Molecular Vibration", J. Am. Chem. Soc. 2020, 142, 6690-6697.
2. Ogoshi, T. Sueto, R.; Yagyu, M.; Kojima, R.; Kakuta, T.; Yamagishi, T.; Doitomi, K.; Tummanapelli, A.; Hirao, H.; Sakata, Y.; Akine, S.; Mizuno, M. "Molecular Weight Fractionation by Confinement of Polymer in One-dimensional Pillararene Channels", Nat. Commun. 2019, 10, 479.
3. Xu, K.; Hirao, H. "Revisiting the Catalytic Mechanism of Mo-Cu Carbon Monoxide Dehydrogenase Using QM/MM and DFT Calculations", Phys. Chem. Chem. Phys. 2018, 20, 18938-18948 (Outside Back Cover).
4. Wang, R.; Ozhgibesov, M.; Hirao, H. "Analytical Hessian Fitting Schemes for Efficient Determination of Force-Constant Parameters in Molecular Mechanics", J. Comput. Chem. 2018, 39, 307-318 (Front Cover).
5. Ghalei, B.; Sakurai, K.; Kinoshita, Y.; Isfahani, A. P.; Song, Q.; Doitomi, K.; Furukawa, S.; Hirao, H.; Kusuda, H.; Kitagawa, S.; Sivaniah, E. "Enhanced Selectivity in Mixed Matrix Membranes for CO2 Capture through Efficient Dispersion of Amine-Functionalized MOF Nanoparticles", Nat. Energy 2017, 2, 17086.
6. Wang, R.; Ozhgibesov, M.; Hirao, H. "Partial Hessian Fitting for Determining Force Constant Parameters in Molecular Mechanics", J. Comput. Chem. 2016, 37, 2349-2359 (Inside Cover).
7. Wu, C.; Yue, G.; Nielsen, C. D.-T.; Xu, K.; Hirao, H.; Zhou, J. S. "Asymmetric Conjugate Addition of Organoboron Reagents to Common Enones Using Copper Catalysts", J. Am. Chem. Soc. 2016, 138, 742-745
8. Cho, K.-B.; Hirao, H.; Shaik, S.; Nam, W. "To Rebound or Dissociate? This is the Mechanistic Question in C–H Hydroxylation by Heme and Nonheme Metal-oxo Complexes", Chem. Soc. Rev. 2016, 45, 1197-1210.
9. Gazi, S.; Ng, W. K. H.; Ganguly, R.; Moeljadi, A. M. P.; Hirao, H.; Soo, H. S. "Selective Photocatalytic C–C bond Cleavage under Ambient Conditions with Earth Abundant Vanadium Complexes", Chem. Sci. 2015, 6, 7130-7142.
10. Xu, K.; Wang, Y.; Hirao, H. "Estrogen Formation via H-Abstraction from the O–H Bond of gem-Diol by Compound I in the Reaction of CYP19A1: Mechanistic Scenario Derived from Multiscale QM/MM Calculations", ACS Catal. 2015, 5, 4175-4179 (included in “Catalysis in Singapore”).
11. Ribeiro, A. J. M.; Yang, L.; Ramos, M. J; Fernandes, P. A.; Liang, Z.-X.; Hirao, H. "Insight into Biological Nitrile Reduction: A QM/MM Study of the Catalytic Mechanism of Nitrile Reductase", ACS Catal. 2015, 5, 3740-3751 (included in “Catalysis in Singapore”).
12. Chuanprasit, P.; Goh, S. H.; Hirao, H. "Benzyne Formation in the Mechanism-Based Inactivation of Cytochrome P450 by 1-Aminobenzotriazole and N-Benzyl-1-Aminobenzotriazole: Computational Insights", ACS Catal. 2015, 5, 2952-2960 (included in “Catalysis in Singapore”).
13. Cui, J.; Li, Y.; Ganguly, R.; Inthirarajah, A.; Hirao, H.; Kinjo, R. "Metal-Free ?-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene", J. Am. Chem. Soc. 2014, 136, 16764-16767.
14. Thellamurege, N. M.; Hirao, H. "Effect of Protein Environment within Cytochrome P450cam Evaluated Using a Polarizable-Embedding QM/MM Method", J. Phys. Chem. B 2014, 118, 2084-2092.
15. Wang, X.; Hirao, H. "ONIOM(DFT:MM) Study of the Catalytic Mechanism of myo-Inositol Monophosphatase: Essential Role of Water in Enzyme Catalysis in the Two-Metal Mechanism", J. Phys. Chem. B 2013, 117, 833-842.
16. Hirao, H.; Morokuma, K. "ONIOM(DFT:MM) Study of 2-Hydroxyethylphosphonate Dioxygenase: What Determines the Destinies of Different Substrates?", J. Am. Chem. Soc. 2011, 133, 14550-14553.
17. Hirao, H.; Morokuma, K. "Insights into the (Superoxo)Fe(III)Fe(III) Intermediate and Reaction Mechanism of myo-Inositol Oxygenase: DFT and ONIOM(DFT:MM) Study", J. Am. Chem. Soc. 2009, 131, 17206-17214.
18. Irie, O.; Kosaka, T.; Ehara, T.; Yokokawa, F.; Kanazawa, T.; Hirao, H.; Iwasaki, A.; Sakaki, J.; Teno, N.; Hitomi, Y.; Iwasaki, G.; Fukaya, H.; Nonomura, K.; Tanabe, K.; Koizumi, S.; Uchiyama, N.; Bevan, S. J.; Malcangio, M.; Gentry, C.; Fox, A. J.; Yaqoob, M.; Culshaw, A. J.; Hallett, A. "Discovery of Orally Bioavailable Cathepsin S Inhibitors for the Reversal of Neuropathic Pain", J. Med. Chem. 2008, 51, 5502-5505.
19. Shaik, S.; Hirao, H.; Kumar, D. "Reactivity Patterns of High-Valent Iron Oxo Species in Enzymes and Synthetic Reagents: A Tale of Many States", Acc. Chem. Res. 2007, 40, 532-542
20. Hirao, H.; Kumar, D.; Thiel, W.; Shaik, S. "Two States and Two More in the Mechanisms of Hydroxylation and Epoxidation by Cytochrome P450", J. Am. Chem. Soc. 2005, 127, 13007-13018
- Academic Publications
PhD (Peking University)
BS (Huazhong University of Science and Technology)
Computational chemistry and biology, multiscale modeling of enzymes，mechanistic study of organic reactions
Dr. Guijuan Cheng received her Bachelor degree from Huazhong University of Science and Technology in 2010. She earned a Ph.D. in Physical Chemistry from Peking University in 2015, carrying out mechanistic studies on organic reactions with combined computational and mass spectrometry method. She then worked at Max-Planck-Institut für Kohlenforschung as a Postdoctoral Fellow, where she carried out mechanistic studies on enzymatic and organic reactions. Since July 2018, Dr. Cheng has been an Assistant Professor in Arieh Warshel Institute of Computational Biology, School of Science and Engineering (SSE), Chinese University of Hong Kong (Shenzhen). Her research interests mainly include QM/MM (quantum mechanics/molecular mechanics) modeling of enzymatic reactions and mechanistic study of chemical reactions by using combined computational and experimental method. She has published 17 papers and 3 articles have been cited more than 100 times which have been rated as ESI Highly Cited Papers. Her Ph.D. theses was named an excellent doctoral thesis of Peking University and was awarded the Springer Thesis Prize.
1. Cheng, G.-J.; Escorcia, A. M.; Rijn, J. F. M..; Thiel, W. MD and QM/MM Studies on CalB-catalyzed Hydrolysis of Propanolol Esters: the Effects of Acyl Moiety. 2018 (in preparation)
2. Cheng, G.-J.; Drosos, N.; Morandi, B.;Thiel, W. Computational Study of B(C6F5)3-Catalyzed Selective Deoxygenation of 1,2-Diols. ACS Catal. 2018, 8, 1697.
3. Escorcia, A. M..; Rijn, J. F. M.; Cheng, G.-J.; Thiel, W. Insight into the Promiscuity of Taxadiene Synthase: A Molecular Dynamic Study. J. Comp. Chem. 2018, 39, 1215.
4. Ma, X.; Mai, S.; Zhou, Y.; Cheng, G.-J.; Song, Q. Dual Role of Ethyl Bromodifluoroacetate in the Formation of Fluorine-containing Heteroaromatic Compounds. Chem. Commun. 2018, 54, 8960.
5. Drosos, N.; Cheng, G.-J.; Ozkal, E.; Cacherat, B.; Thiel, W.; Morandi, B. Catalytic Reductive Pinacol-Type Rearrangement of Unactivated 1,2-diols through a Concerted, Stereoinvertive Mechanism. Angew. Chem. Int. Ed. 2017, 56, 13377.
6. Rummelt, S.; Cheng, G.-J.; Gupta, P.; Thiel, W.; Fürstner, A. Hydroxyl-Directed Ruthenium Catalyzed Alkene/Alkyne Coupling: Increased Scope, Stereochemical Implications and Mechanistic Rationale. Angew. Chem. Int. Ed. 2017, 56, 3599.
7. Jia, J;† Cheng, G.-J.;† Wu, A.; Luan, S. Novel Imprinted Polyethyleneimine Nano-fluorescent Probes with Controllable Selectivity for Recognizing and Adsorbing Metal Ions. RSC Advances 2017, 7, 36048(† equal contribution)
8. Xie, Y.; Cheng, G.-J.; Lee, S.; Thiel, W.; List, B. Catalytic Asymmetric Vinylogous Prins Cyclization: A Highly Diastereo- and Enantioselective Entry to Tetrahydrofurans. J. Am. Chem. Soc. 2016, 138, 14538.
9. Zhong, X.-M.;† Cheng, G.-J.;† P.; Chen, P.; Zhang, X.; Yu, Wu, Y.-D. Mechanistic Study on Pd/Mono-N-protected Amino Acid Catalyzed Vinyl–Vinyl Coupling Reactions: Reactivity and E/Z Selectivity. Org. Lett. 2016, 18, 5240. († equal contribution)
10. Cheng, G.-J.; P.; Chen, P.; Sun, T.-Y.; Zhang, X.; Yu, J.-Q.; Wu, Y.-D. A Combined IM-MS/DFT Study on Pd(MPAA)-Catalyzed Enantioselective C−H Activation: Relay of Chirality through a Rigid Framework. Chem.–Eur. J. 2015, 21, 11180.
11. Cheng, G.-J.; Zhang, X.; Chung, L. W.; Xu, L.; Wu, Y.-D. Computational Organic Chemistry: Bridging Theory and Experiment by Mechanistic Understanding of Chemical Reactions. J. Am. Chem. Soc. 2015, 137, 1706. (ESI highly cited paper)
12. Zhou, F.;† Cheng, G.-J.;† Yang, W.;† Long, Y.; Zhang, S.; Wu, Y.-D.; Zhang, X.; Cai, Q. Enantioselective Formation of Cyano-Bearing All-Carbon Quaternary Stereocenters: Desymmetrization by Copper-Catalyzed N-Arylation. Angew. Chem. Int. Ed. 2014, 53, 9555. († equal contribution)
13. Cheng, G.-J.; Yang, Y.-F.; Liu, P.; Chen, P.; Sun, T.-Y.; Li, G.; Zhang, X.; Houk, K. N.; Yu, J.-Q.; Wu, Y.-D. Role of N-Acyl Amino Acid Ligands in Pd(II)-Catalyzed Remote C–H Activation of Tethered Arenes. J. Am. Chem. Soc. 2014, 136, 894. (ESI highly cited paper)
14. Yang, Y.-F.;† Cheng, G.-J.;† Liu, P.; Chen, P.; Zhang, X.; Yu, J.-Q.; Wu, Y.-D.; Houk, K. N. Palladium-Catalyzed Meta-Selective C–H Bond Activation with a Nitrile-Containing Template: Computational Study on Mechanism and Origins of Selectivity. J. Am. Chem. Soc. 2014, 136, 344. († equal contribution, ESI highly cited paper)
15. Cheng, G.-J.; Song, L.-J.; Yang, Y.-F.; Zhang, X.; Wiest, O.; Wu, Y.-D. Computational Studies on the Mechanism of the Copper-Catalyzed sp3-C-H Cross-Dehydrogenative Coupling Reaction. ChemPlusChem 2013, 78, 943 (Frontispiece paper).
16. Zhu, L.; Zhou, C.; Yang, W.; He, S.; Cheng, G.-J.; Zhang, X.; Lee, C.-S. Formal Syntheses of (±)-Platensimycin and (±)-Platencin via a Dual-Mode Lewis Acid Induced Cascade Cyclization Approach. J. Org. Chem. 2013, 78, 7912.
17. Zhao, K.; Cheng, G.-J.; Yang, H.; Shang, H.; Zhang, X.; Wu, Y.-D.; Tang, Y. Total Synthesis of Incarvilleatone and Incarviditone: Insight into Their Biosynthetic Pathways and Structure Determination. Org. Lett. 2012, 14, 4878.
18. Yang, Y.-F.; Cheng, G.-J.; Zhu, J.; Zhang, X.; Inoue, S.; Wu, Y.-D. Silicon-Containing Formal 4pi-Electron Four-Membered Ring Systems: Antiaromatic, Aromatic, or Not? Chem. Eur. J. 2012, 18, 7516.
Cheng, G.-J. “Mechanistic Studies on Transition Metal-Catalyzed C-H Activation Reactions Using Combined Mass Spectrometry and Theoretical Methods” Springer Theses, 2017, ISBN: 978-981-10-4520-2.
- Academic Publications
Ph.D. (University of Amsterdam)
M.Eng. (Chalmers University of Technology)
B.Eng. (Huazhong University of Science and Technology)
Computational chemistry, computational biology, biomolecular simulations, molecular dynamics, enhanced sampling, path searching, RNA-protein interactions, RNA/DNA interference
Dr. Zhu earned his Ph.D. in Computational Chemistry from University of Amsterdam, where he was a Marie-Curie Early Stage Researcher studying the mechanism of allosteric protein receptors via molecular simulation. He then worked as a Postdoctoral Fellow at The Hong Kong University of Science and Technology with a focus on the integration of enhanced sampling methods with the framework of Markov State Models. Since August 2018, he has been an Assistant Professor in Arieh Warshel Institute of Computational Biology, School of Science and Engineering (SSE), The Chinese University of Hong Kong (Shenzhen).
Dr. Zhu’s current research focuses on RNA-protein interactions, mechanism of RNA/DNA interference and the development of automated path searching methods and other enhanced sampling techniques. He has published 20 papers on recognized journals, such as Physical Review Letters, The Journal of Physical Chemistry Letters, PLOS Computational Biology, Current Opinion in Structural Biology, Journal of Computational Chemistry.
 Longcan Mei, Yanping Zhou, Lizhe Zhu, Changlin Liu, Zhuo Wu, Fangkui Wang, Gefei Hao, Di Yu, Hong Yuan*, and Yanfang Cui*. Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations. International Journal of Molecular Sciences, 19:916–938, 2018.
 Ilona Christy Unarta, Lizhe Zhu, Carmen Ka Man Tse, Peter Pak-Hang Cheung, Jin Yu, and Huang Xuhui. Molecular mechanisms of RNA polymerase II transcription elongation elucidated by kinetic network models. Current Opinion in Structural Biology, 49:54–62, 2018.
 Xiangze Zeng, Lizhe Zhu, Xiaoyan Zheng, Marco Cecchini, and Xuhui Huang. Harnessing complexity in molecular self-assembly using computer simulations. Physical Chemistry Chemical Physics, 20:6767–6776, 2018.
 Matthew Bratkowski, Ilona C. Unarta, Lizhe Zhu, Xuhui Huang, and Xin Liu*. Structural dissection of the TFIIB-Ssu72 interaction implicated in promotor-terminator crosstalk. Journal of Biological Chemistry, 293:1651–1665, 2018.
 Xiangze Zeng, Zhan-Wei Li, Xiaoyan Zheng, Lizhe Zhu, Zhao-Yan Sun, Zhong-Yuan Lu, and Xuhui Huang. Improving the productivity of monodisperse polyhedral cages by the rational design of kinetic self-assembly pathways. Physical Chemistry Chemical Physics, 20:10030–10037, 2018.
 Lizhe Zhu, Hanlun Jiang, Fu Kit Sheong, Xuefeng Cui, Yanli Wang, Xin Gao*, and Xuhui Huang*. Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes. Progress in Biophysics and Molecular Biology, 128:39–46, 2017.
 Siqin Cao, Lizhe Zhu, and Xuhui Huang*. 3DRISM-HI-D2MSA: An improved analytic theory to compute solvent structure around hydrophobic solutes with proper treatment of solute-solvent electrostatic interactions. Molecular Physics, 102:1–11, 2017.
 Wei Wang, Siqin Cao2, Lizhe Zhu2, and Xuhui Huang*. Constructing Markov State Models to elucidate the functional conformational changes of complex biomolecules. Wiley Interdisciplinary Reviews: Computational Molecular Science, page e1343, 2017.
 Luming Meng, Fu Kit Sheong, Xiangze Zeng, Lizhe Zhu, and Xuhui Huang*. Path Lumping: an efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems. The Journal of Chemical Physics, 147(4):044112, 2017.
 Xiaoyan Zheng, Lizhe Zhu, Xiangze Zeng, Luming Meng, Lu Zhang, Dong Wang, and Xuhui Huang*. Kinetics-controlled amphiphile self-assembly processes. The Journal of Physical Chemistry Letters, 8(8):1798–1803, 2017.
 Song Liu, Lizhe Zhu*, Fu Kit Sheong, Wei Wang, and Xuhui Huang*. Adaptive Partitioning by Local Density peaks (APLoD): an efficient density based clustering algorithm for analyzing molecular dynamics trajectories. Journal of Computational Chemistry, 38(3):152–160, 2017.
 Qiushi Zhang, Xiaoyan Zheng, Guowen Kuang, Weihua Wang, Lizhe Zhu, Rui Pang, Xingqiang Shi, Xuesong Shang, Xuhui Huang, Pei Nian Liu*, and Nian Lin*. Singlemolecule investigations of conformation adaptation of porphyrins on surfaces. The Journal of Physical Chemistry Letters, 8(6):1241–1247, 2017.
 Xiangze Zeng, Bin Li, Qin Qiao, Lizhe Zhu, Zhong-Yuan Lu*, and Xuhui Huang*. Elucidating dominant pathways of the nano-particle self-assembly process. Physical Chemistry Chemical Physics, 18:23494–23499, 2016.
 Lizhe Zhu, Hanlun Jiang, Fu Kit Sheong, Xuefeng Cui, Xin Gao, Yanli Wang, and Xuhui Huang*. A flexible domain-domain hinge promotes an induced-fit dominant mechanism for the loading of guide-DNA into Argonaute protein in Thermus thermophilus. The Journal of Physical Chemistry. B, 120(10):2709–2720, 2016.
 Xiaoyan Zheng, Qian Peng*, Lizhe Zhu, Yujun Xie, Xuhui Huang*, and Zhigang Shuai*. Unraveling the aggregation effect on amorphous phase AIE luminogens: a computational study. Nanoscale, 8:15173–15180, 2016.
 Lizhe Zhu, Fu Kit Sheong, Xiangze Zeng, and Xuhui Huang*. Elucidation of the conformational dynamics of multi-body systems by construction of Markov state models. Physical Chemistry Chemical Physics, 18:30228–30235, 2016.
 Hanlun Jiang, Fu Kit Sheong, Lizhe Zhu, Xin Gao, Julie Bernauer*, and Xuhui Huang*. Markov State Models reveal a two-step mechanism of miRNA loading into the human Argonaute protein: selective binding followed by structural re-arrangement. PLOS Computational Biology, 11(7):e1004404, 2015.
 Lizhe Zhu, Peter G. Bolhuis, and Jocelyne Vreede*. The HAMP signal relay domain adopts multiple conformational states through collective piston and tilt motions. PLOS Computational Biology, 9(2):e1002913, 2013.
 Lizhe Zhu, Daan Frenkel, and Peter G. Bolhuis*. Role of fluctuations in ligand binding cooperativity of membrane receptors. Physical Review Letters, 106(16):168103, 2011.
 Maria Werner, Lizhe Zhu, and Erik Aurell*. Cooperative action in eukaryotic gene regulation: Physical properties of a viral example. Physical Review E, 76:061909, Dec 2007.
 Hanlun Jiang, Lizhe Zhu, Amélie Héliou, Xin Gao*, Julie Bernauer*, and Xuhui Huang*. Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches, pages 251–275. Springer New York, New York, NY, 2017.
- Academic Publications
PH. D (BRANDEIS UNIVERSITY)
B.S./M.S. (SHANGHAI JIAO TONG UNIVERSITY)
Computational biology, CADD, AADD
1. Bai, C*; Wang, J; Mondal, D; Du, Y; Ye, R D, Warshel, A* “Exploring the activation process of the β2AR-Gs complex” Journal of the American Chemical Society, 2021, 143, 29, 11044–11051
2. Bai, C; Asadi, M; Warshel, A*; “The catalytic dwell in ATPases is not crucial for movement against applied torque” Nature Chemistry, 2020, 12(12): p. 1187-1192.
3. Bai, C; Warshel, A*; “Critical differences between the binding features of the spike proteins of SARS-CoV-2 and SARS-CoV” The Journal of Physical Chemistry B, 2020, 124(28), 5907-5912
4. Bai, C; Warshel, A*; “Revisiting the protomotive vectorial motion of F0-ATPase” Proceedings of the National Academy of Sciences, U.S.A, 2019, 116, 19484-19489
5. Lee, M; Bai, C; Feliks, M; Alhadeff, R; Warshel, A*; “On the control of the proton current in the voltage-gated proton channel Hv1” Proceedings of the National Academy of Sciences, U.S.A, 2018, 115, 10321-10326
6. Bai, C; Herzfeld, J*. “Chemistry with semi-classical electrons: Reaction trajectories auto-generated by sub-atomistic Force Fields” Chemical Science, 2017, 8, 4203-4210
7. Bai, C; Herzfeld, J*. “Special pairs are decisive in the autoionization and recombination of water” Journal of Physical Chemistry B, 2017, 121, 4213-4219
8. Bai, C; Herzfeld, J*. “Surface propensities of the self-ions of water” ACS Central Science 2016, 2(4) 225-231.
9. Bai, C; Liu, L; Sun H*. “Molecular Dynamics Simulations of Methanol-to-Olefin Reactions in HZSM-5 Zeolite Using a ReaxFF Force Field” Journal of Physical Chemistry C 2012, 116 (12), 7029-7039.
10.Liu, L.; Bai, C.; Sun, H*.; Goddard, W. A*. “Mechanism and Kinetics for the Initial Steps of Pyrolysis and Combustion of 1,6-Dicyclopropane-2,4-Hexyne from ReaxFF Reactive Dynamics” Journal of Physical Chemistry A 2011, 115 (19), 4941-4950.